Activation of the B cell antigen receptor (BCR) requires the efficient activation of the Syk protein tyrosine kinase (PTK). B cells deficient are unable to generate second messengers following receptor engagement. Moreover, mice deficient in syk are unable to develop normal numbers of mature B cells. Hence, the Syk PTK plays a requisite role in the signaling cascade of the BCR. While much has been learned about the Syk PTK, there is still little appreciation or insight into how this kinase regulates B cell activation. In this project (Project 1), we will analyze a novel regulatory mechanism for regulating Syk activity. In addition, we will analyze the dynamics of Syk function using a real time approach combined with a molecular dissection of the signaling parameters which regulate cytoskeletal alterations in B cell morphology following receptor activation. Together, these studies will likely provide novel insights into how Syk regulates B cell activation and also insights into how Syk may regulate receptors expression on other immune cells.